The present invention relates to a novel compound, 1',2'-diacyl-(6R,S)-5,6,7,8-tetrahydro-L-biopterin and a novel compound, 1',2'-diacyl-L-biopterin, and processes for preparing them.
It has been found recently that (6R,S)-5,6,7,8-tetrahydro-L-biopterin and 7,8-dihydro-L-biopterin can be successfully used for a treatment of patients with atypical phenylketonuria (hereinafter referred to as PKU) or with dihydropterin-reductase deficiency [A. B. Schircks, M. Viscontini and J. Schaub, Lancet, 1979, 131; H.-Ch. Curtius, A. Niederwieser, M. Viscontini, A. Otten, J. Schaub, S. Scheibenreiter and H. Schmidt, Clin. Chim. Acta, 93, 251 (1979)].
Though both compounds can conduct an enzymatic hydroxylation of L-tryptophane and L-tyrosine to 5-hydroxytryptophane and DOPA, respectively, in the brain, they have difficulties to cross the blood brain barrier. Therefore neurotransmitter precursors must be given with those compounds during the treatment of both deficiency-diseases.
The present invention has been completed on the basis of the fact that lipophile substances can more readily cross the brain barrier than compounds which possess a greater polarity as (6R,S)-tetrahydro-L-biopterin with its amphoteric nucleus and its free sugar chain.
An object of the present invention is to provide a novel compound, 1',2'-diacyl-(6R,S)-5,6,7,8-tetrahydro-L-biopterin having a low polarity and the same effect as (6R,S)-5,6,7,8-tetrahydro-L-biopterin in treatment of atypical PKU and dihydropterin-reductase deficiency without neurotransmitter precursors.
Another object of the invention is to provide a process for preparing the compound by acylating the free hydroxy groups of the side chain of (6R,S)-tetrahydro-L-biopterin.